In silico prediction and structure-based multitargeted molecular docking analysis of selected bioactive compounds against mucormycosis.
During the second wave of the COVID-19 pandemic, an unusual increase in cases of mucormycosis was observed in India, owing to immunological dysregulation caused by the SARS-CoV-2 and the use of broad-spectrum antibiotics, particularly in patients with poorly controlled diabetes with ketoacidosis to have contributed to the rise, and it has been declared an epidemic in several states of India. Because of the black colouring of dead and dying tissue caused by the fungus, it was dubbed "black fungus" by several Indian media outlets. In this study, attempts were taken to unmask novel therapeutic options to treat mucormycosis disease. Rhizopus species is the primary fungi responsible for 70% of mucormycosis cases. We chose three important proteins from the Rhizopus delemar such as CotH3, Lanosterol 14 alpha-demethylase and Mucoricin which plays a crucial role in the virulence of Mucorales. Initially, we explored the physiochemical, structural and functional insights of proteins and later using AutoDock Vina, we applied computational protein-ligand binding modelling to perform a virtual screening around 300 selected compounds against these three proteins, including FDA-approved drugs, FDA-unapproved drugs, investigational-only drugs and natural bioactive compounds. ADME parameters, toxicity risk and biological activity of those compounds were approximated via in silico methods. Our computational studies identified six ligands as potential inhibitors against Rhizopus delemar, including 12,28-Oxamanzamine A, vialinin B and deoxytopsentin for CotH3; pramiconazole and saperconazole for Lanosterol 14 alpha-demethylase; and Hesperidin for Mucoricin. Interestingly, 12,28-Oxamanzamine A showed a maximum binding affinity with all three proteins (CotH3: - 10.2 kcal/mol Lanosterol 14 alpha-demethylase: - 10.9 kcal/mol Mucoricin: - 8.6 kcal/mol). In summary, our investigation identified 12,28-Oxamanzamine A, vialinin B, deoxytopsentin, pramiconazole, saperconazole and hesperidin as potent bioactive compounds for treating mucormycosis that may be considered for further optimisation techniques and in vitro and in vivo studies. The online version contains supplementary material available at 10.1186/s42269-022-00704-4.


The role of arachidonic acid metabolites in preeclampsia.
Preeclampsia is characterized by imbalances in the production rates of several arachidonic acid metabolites. There is a considerable amount of evidence to indicate that PGI2 production is decreased in preeclampsia. PGI2 is a potent vasodilator, an inhibitor of platelet aggregation, and an inhibitor of uterine contractility. Evidence is accumulating that TX production in preeclampsia is either increased or unchanged so that the ratio of TX to PGI2 favors TX. TX opposes the actions of PGI2 in that it is a potent vasoconstrictor, a stimulator of platelet aggregation, and a stimulator of uterine contractility. Therefore, an imbalance of increased TX/decreased PGI2 production can account for the major clinical symptoms of preeclampsia. There is now preliminary evidence that the placenta produces lipoxygenase, as well as cyclooxygenase compounds. The hydroxyeicosatetranoic acids (5-HETE, 12-HETE, 15-HETE) and LTB4 have been identified as placental products. The preeclamptic placenta appears to be deficient in the 5- and 12-lipoxygenase enzymes, as indicated by placental production of 5-HETE and 12-HETE. Little is known about the regulation of arachidonic acid metabolites in normal or preeclamptic pregnancies. Steroids are known to affect cyclooxygenase product production. Progesterone, for example, inhibits PGI2 production. Although circulating and urinary concentrations of progesterone do not differ between normal and preeclamptic pregnancies, there is one report that placental progesterone concentrations are higher in preeclampsia; this may partially explain the decreased placental production of PGI2. There is a considerable amount of evidence in various tissues that regulatory interactions exist between the cyclooxygenase and lipoxygenase metabolites of arachidonic acid, but the role of these interactions in preeclampsia is not known. There is still much to be learned about the etiology of preeclampsia, but it is certain that aberrations in the production of arachidonic acid metabolites play an important role. It is likely that the effective treatment of preeclampsia will come from understanding the regulation of the arachidonic acid metabolites during pregnancy, and, therefore, the ability to specifically treat the production imbalances that characterize this disorder.


Auraptene Has Antiviral Activity against Human Coronavirus OC43 in MRC-5 Cells.
Auraptene (7-geranyloxycoumarin) is the abundant prenyloxycoumarin found in the fruits of Citrus spp. Auraptene has a variety of pharmacological and therapeutic functions, such as anticancer, antioxidant, immunomodulatory, and anti-inflammation activities, with excellent safety profiles. In this study, we evaluated the anticoronaviral activity of auraptene in HCoV-OC43-infected human lung fibroblast MRC-5 cells. We found that auraptene effectively inhibited HCoV-OC43-induced cytopathic effects with 4.3 μM IC50 and 6.1 μM IC90, resulting in a selectivity index (CC50/IC50) of >3.5. Auraptene treatment also decreased viral RNA levels in HCoV-OC43-infected cells, as detected through quantitative real-time PCR, and decreased the expression level of spike proteins and nucleocapsid proteins in virus-infected cells, as detected through the Western blot analysis and immunofluorescence staining. Time-of-addition analysis showed auraptene's inhibitory effects at the post-entry stage of the virus life cycle; however, auraptene did not induce the antiviral interferon families, IFN-α1, IFN-β1, and IFN-λ1. Additionally, auraptene-treated MRC-5 cells during HCoV-OC43 infection decreased the MMP-9 mRNA levels which are usually increased due to the infection, as auraptene is a previously reported MMP-9 inhibitor. Therefore, auraptene showed antiviral activity against HCoV-OC43 infection, and we suggest that auraptene has the potential to serve as a therapeutic agent against human coronavirus.


Women and AIDS: the ethics of exaggerated harm.
This article examines the way in which some biomedical ethicists have constructed sexually transmitted AIDS as a significant threat to women's health. We demonstrate that the familiar claim that 'women are the fastest growing group' -- whether of HIV-infected or of AIDS patients -- is misleading because it obscures the distinction between proportional rate of growth and absolute increase. Feminist ethicists have suggested that misogyny of a male dominated health care system has led to underreporting of women AIDS cases in order to support these feminists' claim of AIDS being a real threat to women's health. Given the apparent rarity of tertiary transmissions of AIDS, the assertion that most or even many women are at significant risk for AIDS seems wrong. Particularly disturbing in this campaign is the fact that the theme of 'risky sex' has been extended all the way to lesbians, even though their risk to acquire AIDS sexually is non-existent to miniscule. We argue that actual harm is done to women by this exaggeration of their risk of contracting AIDS sexually. The scare has led to misappropriations of scarce health care funds. AIDS disproportionately affects women who inject drugs, and who suffer other diseases, poverty and malnutrition. It would have been better to concentrate health care efforts in this area instead of 'educating' women not at risk for AIDS how to prevent the acquisition of this disease. Unjustifiable AIDS anxiety has been created in women and has resulted in millions of unnecessary HIV-tests, and many broken relationships. This anxiety has inevitably reduced the pleasure of having sex for many women. We reject the kind of 'victim ideology' that lies at the heart of this strategy which has, unfortunately, been supported by a number of influential feminist ethicists.


Comparison of three computer-administered cognitive tasks as putative endophenotypes of schizophrenia.
It has been repeatedly demonstrated that individuals with schizotypal personality features (SPF) exhibit similar endophenotypic traits as persons with schizophrenia. Less research has compared the relative sensitivity of different endophenotypes in the same sample of individuals with SPF. Fourteen university students with SPF (mean age 20.5+/-1.6; 43% male) and 26 controls (mean age 20.3+/-1.1; 31% male) were defined by the Abbreviated Schizotypal Personality Questionnaire (SPQ-B). All participants reported no known biological relative with schizophrenia. Participants completed three computer-administered cognitive tasks: a 6-min degraded-stimuli A-X Continuous Performance Test (CPT), the Wisconsin Card Sort Test (WCST), and a Span of Apprehension (SOA) task (6- and 12-letter arrays). On the CPT, only omission errors resulted in a statistically significant group difference, U=115.5, p=.05, Cohen's d=0.54 (medium effect size), with the SPF group (mean errors: 3.43+/-3.28) making more omission errors than controls (mean errors: 1.88+/-2.66). Notably, 46% of the controls had no omission errors, compared to 14% of the SPF group. The only SPQ-B factor score to show a statistically significant linear relationship with CPT omission errors was the Cognitive-Perceptual factor (rs=.33, p=.04). Group differences on performance indices from the SOA and WCST did not approach statistical significance. Based on performance from the community-identified schizotypes, results suggest that performance on the CPT may represent a more robust endophenotype of schizophrenia, compared to the SOA and WCST.


Neighbor effect: penumbra-dose exposed neighbor cells contribute to the enhanced survival of high-dose targeted cells.
In the last decade, new types of 'bystander effect' have been suggested by multiple research groups and have been challenged by others. In this study, we explored a new type of bystander effect, which has been defined in previous studies as the enhancement of the survival of high-dose targeted cells due to the penumbra-dose exposed neighbor cells. Intensity-modulated radiation therapy, which is the most widely used treatment modality, generates local regions of gradient doses between targeted and shielded cells throughout the treatment volume; therefore, we were urged to ascertain whether the new type of effect is real and to suggest a revised treatment planning. Cellular responses under non-uniform beam fields were observed in rat gliosarcoma cells, rat diencephalon cells, and mouse endothelial cells. The cells were irradiated with 200 kVp X-rays in two types: (1) all the cells in the flask were exposed to the X-ray beam (whole-beam exposure) and (2) half of the cells in the flask were exposed to the beam while the other half, or neighbor cells, were shielded from the beam (half-beam exposure). Target cells were exposed to 1, 2, 4, 6, 8, and 10 Gy, and the penumbra dose was approximately 10%-20% of the target dose. Target cells survived high-dose (> 6 Gy) radiation exposures better under half-beam exposure with the low penumbra-dose exposed neighbor cells around than under whole-beam exposure. The survival of the targeted cells from half-beam exposure was reduced when the radiation self-conditioned medium was replaced with a fresh one immediately after irradiation. Survival was further reduced when the targeted cells were harvested immediately after irradiation and incubated in new dishes with fresh culture media until the colony was counted. We have collected data of good statistics by several post-irradiation treatments of targeted cells to ascertain that the new type of bystander effect is real. The low penumbra-dose exposed neighbor cells benefited the survival of the high-dose targeted cells.


Inhibition of endoplasmic reticulum stress signaling pathway: A new mechanism of statins to suppress the development of abdominal aortic aneurysm.
Abdominal aortic aneurysm (AAA) is a potentially lethal disease with extremely poor survival rates once the aneurysm ruptures. Statins may exert beneficial effects on the progression of AAA. However, the underlying mechanism is still not known. The purpose of the present study is to investigate whether statin could inhibit AAA formation by inhibiting the endoplasmic reticulum (ER) stress signal pathway. A clinically relevant AAA model was induced in Apolipoprotein E-deficient (ApoE-/-) mice, which were infused with angiotensin II (Ang II) for 28 days. These mice were randomly divided into following 4 groups: saline infusion alone; Ang II infusion alone; Ang II infusion plus Atorvastatin (20mg/kg/d); and Ang II infusion plus Atorvastatin (30mg/kg/d). Besides, another AAA model was induced in C57 mice with extraluminal CaCl2, which were divided into 3 groups: sham group, CaCl2-induced AAA group, and CaCl2-induced AAA plus atorvastatin (20mg/kg/d) group. Then, aortic tissue was excised for further examinations, respectively. In vitro studies, Ang II with or without simvastatin treatment were applied to the vascular smooth muscle cells (VSMCS) and Raw 264.7 cells. The ER stress signal pathway, apoptosis and inflammatory response were evaluated by in vivo and in vitro assays. We found that higher dose of atorvastatin can effectively suppress the development and progression of AAA induced by Ang II or CaCl2. Mechanistically, the activation of ER stress and inflammatory response were found involved in Ang II-induced AAA formation. The atorvastatin infusion significantly reduced ER stress signaling proteins, the number of apoptotic cells, and the activation of Caspase12 and Bax in the Ang II-induced ApoE-/- mice, compared with mice treated by Ang II alone. Furthermore, proinflammatory cytokines such as IL-6, IL-8, IL-1β were all remarkably inhibited after atorvastatin treatment. In vitro, the inhibitory effect of simvastatin on the ER stress signal pathway could be observed in both vascular smooth muscle cells and macrophages, and these inhibitory effects of statin were in a dose-dependent manner. In addition, apoptosis was induced with Ang II treatment. The maximal inhibitory effect of simvastatin on apoptosis was observed at 10 μmol/l. We conclude that higher dose of statin can effectively suppress the development of AAA, and reduce ER stress, ER stress-associated apoptosis signaling pathways, and inflammatory response. These findings reveal a new mechanism underlying the inhibitory effect of statin on AAA formation/progression.


Docetaxel-based combination therapy for castration-resistant prostate cancer.
Once castration resistance is documented and secondary hormone therapy is ineffective, standard treatment of metastatic prostate cancer is docetaxel, with bisphosphonates and radiopharmaceuticals administered to treat bone symptoms. To improve outcomes, numerous studies have evaluated docetaxel in combination with other agents. Here, results for docetaxel-based combination therapy in castration-resistant prostate cancer (CRPC) are reviewed. Relevant studies were identified in databases of published literature, clinical trials, and conference abstracts using the search terms docetaxel and prostate, with additional searches carried out for identified agents. Numerous classes of agents have been combined with docetaxel in phase II studies in CRPC, including tyrosine kinase inhibitors, antiangiogenic agents, bone-targeted agents, BCL-2 inhibitors, chemotherapies, immunologic agents, and vitamin D analogs. In several cases, promising rates of prostate-specific antigen response, tumor response, and survival have been reported. However, some combinations have caused increased toxicity. Phase III trials with docetaxel plus GVAX or DN-101 were terminated because of lower survival; phase III trials with docetaxel plus bevacizumab, aflibercept, dasatinib, zibotentan, atrasentan, or lenalidomide are ongoing. Docetaxel-based doublet therapy remains an active investigational strategy in CRPC. Further phase III data are awaited to determine whether survival can be extended compared with docetaxel alone.


Coarse-Grained Modeling of Polyethylene Melts: Effect on Dynamics.
The distinctive viscoelastic behavior of polymers results from a coupled interplay of motion on multiple length and time scales. Capturing the broad time and length scales of polymer motion remains a challenge. Using polyethylene (PE) as a model macromolecule, we construct coarse-grained (CG) models of PE with three to six methyl groups per CG bead and probe two critical aspects of the technique: pressure corrections required after iterative Boltzmann inversion (IBI) to generate CG potentials that match the pressure of reference fully atomistic melt simulations and the transferability of CG potentials across temperatures. While IBI produces nonbonded pair potentials that give excellent agreement between the atomistic and CG pair correlation functions, the resulting pressure for the CG models is large compared with the pressure of the atomistic system. We find that correcting the potential to match the reference pressure leads to nonbonded interactions with much deeper minima and slightly smaller effective bead diameter. However, simulations with potentials generated by IBI and pressure-corrected IBI result in similar mean-square displacements (MSDs) and stress autocorrelation functions G(t) for PE melts. While the time rescaling factor required to match CG and atomistic models is the same for pressure- and non-pressure-corrected CG models, it strongly depends on temperature. Transferability was investigated by comparing the MSDs and stress autocorrelation functions for potentials developed at different temperatures.


Identification of the multimorbidity training needs of primary care professionals: Protocol of a survey.
Current epidemiological situation has prompted the consideration of multimorbility (MM) as a prevalent condition, influenced by age, educational level and social support, related to unfavorable social and health determinants. Primary Care (PC) has a key role in its approach but further training of professionals in MM is required. The evidence on the effectiveness of training interventions in MM is still limited. Knowing the experiences, opinions and training needs of professionals is essential to enhance training interventions. Identify perceived training needs by PC health professionals (doctors and nurses) in MM and polypharmacy. Design: Cross-sectional study based on an online survey (anonymous-ad hoc questionnaire). Participants and recruitment: 384 doctors and nurses working in healthcare centers and out-of-hospital emergencies of the Spanish National Health System. Non-probabilistic convenience sampling via email addressed to Health Institutions, and social networks. Demographic characteristics and professional profile data (close-ended and multiple-choice questions) will be collected. Open-ended questions will be used to identify training needs, difficulties and resources about MM; required skills to care patients with MM will be assessed using a 4-item ordinal scale. Coding of data prior to analysis. Descriptive statistical analysis, participation and completion rates of the questionnaire and estimation of absolute and relative frequencies and 95% confidence intervals in close-ended questions. Content analysis with inductive methodology in open-ended questions. Ethics: Ethical approval, Online informed consent. The identification of training needs of health professionals who care for patients with MM will be necessary data for developing highly effective training activities.


[Data on occupational diseases among health personnel and workers of medicine-related industry in St. Petersburg].
A total of 105 occupational morbidity cases in health service workers were analyzed among 2914 occupational morbidity cases in St. Petersburg. Most of those cases among health service workers were drug allergies, tuberculosis was relatively rare. The study revealed low efficiency of periodic medical examinations conducted for early diagnosis of occupational diseases. Alarming evidence is rare diagnosis such occupational diseases as hands overstrain, strained working posture, disorders due to physical factors, viral B hepatitis.


Myelin proteolipid protein expressed in COS-1 cells is targeted to actin-associated surfaces.
The compact myelin sheath represents one of the largest expanses of membrane-membrane contact in the body and, in the central nervous system, requires the myelin proteolipid protein (PLP) for assembly. To determine whether the molecular properties of PLP promote membrane adhesion and direct its subcellular localization in the absence of oligodendrocyte-specific targeting mechanisms, PLP was expressed in COS-1 fibroblasts. Immunofluorescence staining indicated that PLP was translated effectively, transited the rough endoplasmic reticulum and Golgi apparatus, was delivered to the cell surface, and was endocytosed. In the plasma membrane, the PLP distribution was patchy and only sporadically coincided with sites of membrane-membrane contact between PLP-expressing cells. PLP was not randomly distributed, however, but correlated closely with microfilament locations in leading edge membranes and microvilli, as demonstrated by phalloidin double labeling. Our results indicate that even in non-myelinating cells, PLP can be concentrated in membranes associated with movement and growth, and suggest possible roles for the actin cytoskeleton in PLP localization. As PLP, DM20, and the DM20-like M6 protein all associate with actin-enriched membranes, this may be a common feature of PLP/DM20 gene family members.


From the city to the Lake: loadings of PCBs, PBDEs, PAHs and PCMs from Toronto to Lake Ontario.
Loadings from Toronto, Canada to Lake Ontario were quantified and major sources and pathways were identified, with the goal of informing opportunities for loading reductions. The contaminants were polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs) and polycyclic musks (PCMs). Loadings were calculated from measured concentrations for three major pathways: atmospheric processes, tributary runoff, and wastewater treatment plant (WWTP) effluents. Although atmospheric deposition to the Great Lakes has received the greatest attention, this was the dominant loading pathway for PCBs only (17 ± 5.3 kg/y or 66% of total loadings). PCB loadings reflected elevated urban PCB air concentrations due to, predominantly, primary emissions. These loadings contribute to consumption advisories for nearshore fish. PBDE loadings to the lake, again from mainly primary emissions, were 48% (9.1 ± 1.3 kg/y) and 42% (8.0 ± 5.7 kg/y) via tributaries and WWTPs, respectively, consistent with emissions deposited and subsequently washed-off of urban surfaces and emissions to the sewage system. PAHs loadings of 1600 ± 280 kg/y (71%) from tributaries were strongly associated with vehicle transportation and impervious surfaces. PCM loadings were 83% (±140 kg/y) from WWTP final effluent, reflecting their use in personal care products. Opportunities for source reduction lie in reducing the current inventories of in-use PCBs and PBDE-containing products, reducing vehicle emissions of PAHs and use of PAHs in the transportation network (e.g., pavement sealants), and improving wastewater treatment technology.


Broad spectrum oral amoxycillin in acute respiratory tract infections.
The clinical outcome of 143 patients presenting with acute respiratory tract infection and treated with oral amoxycillin is described. A clinical success rate of 92% was observed after 1 week's therapy with only one patient deteriorating whilst on treatment. Side-effects were mild and limited to 7% of patients.


Microbial Profiling in Experimentally Induced Biofilm Overgrowth Among Patients With Various Periodontal States.
This study measures microbial composition changes during biofilm overgrowth and subsequent removal among patients with various states of periodontal disease. In this prospective cohort study, 175 participants with various periodontal states (five biofilm-gingival interface [BGI] groups) abstained from oral hygiene while using an acrylic stent. At day 21, participants reinstituted oral hygiene and were followed for 4 weeks. Clinical parameters were recorded, and subgingival plaque samples were analyzed at baseline, peak of induction (day 21), and resolution using 16S rRNA probes (human oral microbe identification microarray [HOMIM]). Using the change score (peak at induction minus baseline) for bleeding on probing and probing depth (PD), the patients were separated into high and low clinical responders. At baseline, synergistetes were more abundant in moderate and severe periodontitis (BGI-P2 and -P3) compared to mild periodontitis (BGI-P1), health (BGI-H), and gingivitis (BGI-G) (P = 0.005). Overall, at day 21 there was an increase in HOMIM scores of firmicutes (P ≤0.001), fusobacteria (P = 0.003), proteobacteria (P ≤0.001), synergistetes (P = 0.04), and bacteroidetes (P ≤0.001). At resolution, these phyla returned to baseline, except for synergistetes. Levels of synergistetes were significantly higher at day 21 (P ≤0.0001) and resolution (P = 0.0002) for high clinical responders compared to low responders. The association of synergistetes as a baseline predictor of incident PD increase, as well as the higher levels at day 21, indicates a pathogenic role for these organisms in disease progression in addition to the previously characterized fusobacteria, proteobacteria, firmicutes, and bacteroidetes.


Free hand technique of cervical lateral mass screw fixation.
We introduce a simple free hand technique with great ease of application, without angles, measures or degrees, and without any fluoroscopic guidance. It is a safe and reproducible technique. We present our preliminary experience with the use this technique, with inimitable simplicity. The primary aim of the procedure was to achieve adequate screw trajectory in an apparent challenging ease which is reproducible with a good outcome. Lateral mass screw fixation is used for posterior subaxial cervical fixation. It was described by Louis and Magerl, then by Anderson, An, and Ebraheim et al. Each one described the procedure with a unique screw entrance point and trajectory. This study is a prospective case study of 45 patients who underwent subaxial cervical lateral mass screw fixation. The screws were inserted using a free hand method. The described free hand technique was found to minimize the morbidity associated with other techniques without compromising the quality of fixation. Surgical experiences with this technique found it equally safe, rapid, easy, and reproducible.


Development of a research-based hospital model in Korea.
Noting the increasing public attention on healthcare, Korean society has shown greater attention to the significance of the health technology (HT) development. In order to promote HT competitiveness, the role of research-based hospitals (RBHs), in producing new ideas as well as utilizing final outcomes, has grown increasingly significant. Despite high quality healthcare professionals, state-of-the-art equipment, and well-developed information technology, few hospitals in Korea are successful leaders in HT development. In order to understand HT research and development (R&D) programs in Korea as well as hospital-based R&D investment performance, this paper has analyzed a recent three-year R&D investment of the Korean government. In addition, a survey on how to promote RBHs in Korea has been proceeded through adopting the Delphi method. Several model cases of RBHs abroad have also been studied to understand key success factors in formulating a development model of RBHs in Korea. This paper proposes suggestions for the promotion of RBHs in Korea: systematic reform related to the hospitals, reinforcement of the infrastructure of the hospitals, empowering human resources and policy framework to support the hospitals.


Clinical implications of the ethane in exhaled breath in patients with acute paraquat intoxication.
Pulmonary fibrosis due to lipid peroxidation is a major symptom of paraquat intoxication. Ethane in the expired breath (exEth) reflects lipid peroxidation and may be a measure of the damage effected by oxygen radicals in acute lung injury. The purpose of this study was to evaluate the clinical efficacy of exEth as a measure of exposure to paraquat and as an indicator of lung damage. Exposure levels were evaluated by the amount ingested, semiquantitative measurement of urine paraquat levels, and plasma paraquat concentration. End-tidal breath was collected for measurement of ethane 24 h after paraquat ingestion. Renal function and blood gas analyses were conducted on the same day as the breath collection, and the final clinical outcome was defined as either recovery or death. Associations between exEth and paraquat exposure profiles and clinical outcomes were assessed using linear regression models. Twenty-one patients poisoned by paraquat were selected for the study during 2001 and 2002. exEth could not be used as a predictor of laboratory parameters such as Pa(O2), Pa(CO2), serum creatinine, and lung injury (as graded by high-resolution CT). A logistical analysis revealed that only the amount of paraquat ingested was a significant predictor of fatality (p = 0.021). The strength of the association between exEth and fatality was unaffected by the addition of potential confounders such as age, sex, and time interval and paraquat concentration. exEth cannot be used as either an independent predictor of survival or a specific marker of lung injury in patients with acute paraquat poisoning.


A systematic review on ankle injury and ankle sprain in sports.
This article systematically reviews epidemiological studies on sports injury from 1977 to 2005 in which ankle injury was included. A total of 227 studies reporting injury pattern in 70 sports from 38 countries were included. A total of 201,600 patients were included, with 32,509 ankle injuries. Ankle injury information was available from 14,098 patients, with 11 847 ankle sprains. Results show that the ankle was the most common injured body site in 24 of 70 included sports, especially in aeroball, wall climbing, indoor volleyball, mountaineering, netball and field events in track and field. Ankle sprain was the major ankle injury in 33 of 43 sports, especially in Australian football, field hockey, handball, orienteering, scooter and squash. In sports injuries throughout the countries studied, the ankle was the second most common injured body site after the knee, and ankle sprain was the most common type of ankle injury. The incidence of ankle injury and ankle sprain was high in court games and team sports, such as rugby, soccer, volleyball, handball and basketball. This systematic review provides a summary of the epidemiology of ankle injury in sports.


From randomised clinical trials to clinical practice : a pragmatic cost-effectiveness analysis of Paclitaxel in first-line therapy for advanced ovarian cancer.
Paclitaxel plus cisplatin is considered to be the standard first-line therapy for advanced ovarian cancer. Previous to this study, economic data on this combination resulted from randomised clinical trials (RCTs). Therefore, the objective of this study was to compare the clinical and economic outcomes associated with paclitaxel-cisplatin (PC) and cyclophosphamide-cisplatin (CC) regimens using a pragmatic perspective based on daily clinical practice in a French university hospital. A retrospective cost-effectiveness analysis, from the hospital-payer perspective, was carried out as a before-after case study in fifty-nine consecutive women with verified International Federation of Gynaecology and Obstetrics (FIGO) stage II, III or IV ovarian cancer treated between 1995 and 2000. Median overall survival (OS) was used as the primary endpoint. The quality-adjusted time was assessed by the quality-adjusted time without symptoms or toxicity (Q-TWiST) method. Direct medical costs were collected for each patient. Monetary values for French prices in the year 2000 were used and converted to US dollars using an exchange rate of USD 1 = 7 French francs. Several univariate sensitivity analyses were carried out varying unit costs, medical practices and administration of paclitaxel. The incremental cost of the PC regimen was USD 10,716 per patient. OS and quality-adjusted time were improved by 10.8 and 9.3 months with the PC regimen. The cost per life-year gained and per added QALY were USD 11,907 and USD 13,827, respectively. The robustness of the results was confirmed in sensitivity analyses. Our study suggests that PC may be a cost-effective regimen for advanced ovarian cancer in a French university hospital setting. We reported higher incremental costs and lower clinical benefits than RCT-based findings, suggesting that RCT-based findings were clearly balanced by our pragmatic approach based on clinical practices. Observational studies can provide complementary and balanced data for decision making.


Roles of Reexamination of Core Beliefs and Rumination in Posttraumatic Growth Among Parents of Children With Cancer: Comparisons With Parents of Children With Chronic Disease.
Studies have indicated that the impact of a traumatic experience can be negative and can provide the opportunity to experience psychological growth, known as posttraumatic growth (PTG). To evaluate the role of cognitive processing in PTG among parents of childhood cancer survivors (CCSs) based on the PTG theoretical model. We compared the model between parents of SCC and parents of children with chronic disease (CCDs) to determine how the role of cognitive processing in PTG is different depending on the children's illness. Final sample consisted of 78 parents of CCSs and 44 parents of CCDs. The survey included standardized measurements assessing reexamination of core beliefs, intrusive and deliberate rumination, posttraumatic stress symptoms, and PTG. The hypothetical relationships among the variables were tested by covariance structure analysis. Posttraumatic growth among parents of CCSs had significantly strong association with reexamination of core beliefs, but not with deliberate rumination. Reexamination of core beliefs was significantly more likely to foster PTG among parents of CCSs, whereas deliberate rumination was significantly more likely to be associated with PTG among parents of CCDs. For parents of CCSs, reexamination of core beliefs had a greater impact on PTG than deliberate rumination. Our results suggest that support should focus on the process of reexamining core beliefs in facilitating PTG among parents of CCSs. Nurses should provide parents of CCSs with reassurance regarding their experiences of the reexamination of core beliefs, which will likely lead to PTG.


Nordic Seaweed and Diabetes Prevention: Exploratory Studies in KK-Ay Mice.
The global epidemic of type 2 diabetes (T2D) is a challenging health problem. Lifestyle changes, including nutrition therapy, areimportant for the prevention and management of T2D. Seaweeds contain several bioactive substances with potential health properties and may be a low-cost alternative functional food in the prevention of T2D. The aim of this study was to explore the preventive effects of dried Nordic seaweed species on diabetes in an animal model of T2D. Fiftymale KK-Ay mice were randomly assigned to one of four diets: control diet (chow) or diets supplemented with Alaria esculenta (AE), Saccharina latissima (SL), or Palmaria palmata (PP). The effect of the interventions on the progression of T2D was monitored over 10 weeks and evaluated by circulating glucose, glycated hemoglobin (HbA1c), insulin, glucagon, and lipid levels. The SL group had significantly lower bodyweight, lower HbA1c and insulin levels, as well as higher high density lipoprotein (HDL) cholesterol levels after the 10-week intervention than the control group. At the end of the study, the control group had significantly higher HbA1c (p < 0.001) than all of the seaweed groups. All seaweed groups improved HbA1C compared to control and Saccharinalatissima seaweed had concomitantly beneficial effects on glycemic control and lipid levels in KK-Ay diabetic mice.


Osteoarthritis. How to manage pain and improve patient function.
Osteoarthritis (OA) typically affects persons over age 60 and is often associated with pain and disability. Weight-bearing joints are most commonly affected. The goal of treatment is to minimize pain and its impact on patient function and quality of life. Patient education, psychological support, weight control, exercise, heat/cold application, and use of assistive devices are safe nonpharmacologic approaches. Pharmacologic therapies include acetaminophen, selected NSAIDs, and other analgesics, including opioids for moderate to severe pain. Topical agents, complementary products, viscosupplementation, and surgery may be useful in an individualized treatment plan.


Expression of Hypoxia-Inducible Factor 1α (HIF-1α) and Genes of Related Pathways in Altered Gravity.
Immune system deterioration in space represents a major risk, which has to be mitigated for exploration-class missions into the solar system. Altered gravitational forces have been shown to regulate adaptation processes in cells of the immune system, which are important for appropriate risk management, monitoring and development of countermeasures. T lymphocytes and cells of the monocyte-macrophage system are highly migratory cell types that frequently encounter a wide range of oxygen tensions in human tissues and in hypoxic areas, even under homeostatic conditions. Hypoxia-inducible factor 1 and 2 (HIF's) might have an important role in activation of T cells and cells of the monocyte-macrophages system. Thus, we investigated the regulation of HIF-dependent and, therefore, hypoxia-signaling systems in both cell types in altered gravity and performed transcript and protein analysis from parabolic flight and suborbital ballistic rocket experiments. We found that HIF-1α and HIF-1-dependent transcripts were differently regulated in altered gravity, whereas HIF-1α-dependent gene expression adapted after 5 min microgravity. Inter-platform comparisons identified PDK1 as highly responsive to gravitational changes in human U937 myelomonocytic cells and in Jurkat T cells. We suggest HIF-1 as a potential pharmacological target for counteracting immune system deterioration during space flight.


Dopamine D2 receptor and β-arrestin 2 mediate Amyloid-β elevation induced by anti-parkinson's disease drugs, levodopa and piribedil, in neuronal cells.
Although levodopa is the first-line medication for the treatment of Parkinson's disease (PD) showing unsurpassable efficiency, its chronic use causes dyskinesia. Accordingly, dopamine agonists are increasingly employed as monotherapy or in combination with levodopa to reduce the risk of motor complications. It is well recognized that patients with PD often exhibit cognitive deficits. However, clinical and animal studies assessing the effects of dopaminergic medications on cognition are controversial. Amyloid-β (Aβ) is one of the major hallmarks of Alzheimer's disease (AD), leading to progressive memory loss and cognitive deficit. Interestingly, the abnormal accumulation of Aβ is also detected in PD patients with cognitive deficits. Evidence indicated that levodopa induced a mild increase of Aβ plaque number and size in the brain of AD mouse. However, the underlying mechanism is unclear. Here we present that both levodopa and piribedil enhance the generation of Aβ and the activity of γ-secretase in human neuronal cells and primary neurons isolated from AD mouse. This effect was reduced by either the antagonism or the knockdown of dopamine D2 receptor (D2R). We further showed that in the cells expressing β-arrestin 2-biased D2R mutant, piribedil promoted cellular Aβ production to the extent comparable to the wild-type D2R whereas this activity was absent in those with G protein-biased D2R mutant. Moreover, the knockdown of β-arrestin 2 attenuated the increases of Aβ generation and γ-secretase activity mediated by levodopa or piribedil. Thus, our study suggests that targeting D2R-mediated β-arrestin function may have potential risk in the modulation of Aβ pathology.


Ventilator-induced barotrauma in critically ill patients with COVID-19: a retrospective observational study.
Background: Ventilator-induced Barotrauma is a complication of intubation that is associated with high driving pressures and positive end-expiratory pressure use. We attempt to determine the incidence of barotrauma in intubated patients with SARS-CoV-2 infection. Methods: Retrospective observation case series of patients with SARS-CoV-2 infection who were intubated in the ICU. Data were collected for a total of 3 months from electronic health records on patient's age, sex, BMI, incidence of barotrauma, total length of intubation and outcome. Results: Ninteen out of the 100 included patients developed barotrauma as defined by radiographic evidence of pneumothorax, pneumomediastinum or subcutaneous emphysema. The average BMI of patients with barotrauma was 32.06 kg/m2 with an average age of 56.84 years and 9 patients being classified as obese (BMI ≥30 kg/m2). Fourteen out of 19 patients (73%) with barotrauma were intubated for 10 or more days with a median of 16.52 days. The overall mortality rate was noted to be 92% amongst intubated patients. Conclusion: Rate of barotrauma in COVID-19 intubated patients was noted to be 19% in our study, which is on par with the rate of ventilator-induced barotrauma with the previous SARS virus-associated ARDS, and higher than that of the general population with ARDS. Patients who developed barotrauma were also noted to be intubated for a significantly longer duration (16.52 days) as compared to their non-barotrauma counterparts. These findings suggest a need for more data and randomized studies to establish appropriate ventilator management strategies for patients with lung injury associated with COVID-19.


Climate change and health informatics: pilot survey of perspectives across the field.
Establish a baseline of informatics professionals' perspectives on climate change and health. Anonymized survey sent to 9 informatics listservs March 31, 2022 to April 15, 2022. N = 85 participants completed part or all of survey. Majority of participants worked at hospitals with 1000+ employees (73%) in urban areas (60%) in the United States. Respondents broadly reported general understanding of climate change and health (51%), but 71% reported unfamiliarity with technologies that could help clinicians and informaticians address the impacts of climate change. Seventy-one percent of surveyed wanted climate-driven environmental health information included in EHRs. Seventy-six percent of respondents reported that informaticians should be involved in institutional decarbonization. Seventy-eight percent of respondents felt that it was extremely, very, or moderately important to receive education on climate change. General consensus on need to engage informaticians in climate change response, but gaps identified in knowledge dissemination and tools for adaptation and mitigation. Informaticians broadly concerned about climate change and want to be engaged in efforts to combat it, but further education and tool development needed.


Ghrelin protection against lipopolysaccharide-induced gastric mucosal cell apoptosis involves constitutive nitric oxide synthase-mediated caspase-3 S-nitrosylation.
Ghrelin, a peptide hormone produced mainly in the stomach, has emerged as an important modulator of the inflammatory responses that are of significance to the maintenance of gastric mucosal integrity. Here, we report on the role of ghrelin in controlling the apoptotic processes induced in gastric mucosal cells by H. pylori lipopolysaccharide (LPS). The countering effect of ghrelin on the LPS-induced mucosal cell apoptosis was associated with the increase in constitutive nitric oxide synthase (cNOS) activity, and the reduction in caspase-3 and inducible nitric oxide synthase (NOS-2). The loss in countering effect of ghrelin on the LPS-induced changes in apoptosis and caspase-3 activity was attained with Src kinase inhibitor, PP2, as well as Akt inhibitor, SH-5, and cNOS inhibitor, L-NAME. Moreover, the effect of ghrelin on the LPS-induced changes in cNOS activity was reflected in the increased cNOS phosphorylation that was sensitive to SH-5. Furthermore, the ghrelin-induced up-regulation in cNOS activity was associated with the increase in caspase-3 S-nitrosylation that was susceptible to the blockage by L-NAME. Therefore, ghrelin protection of gastric mucosal cells against H. pylori LPS-induced apoptosis involves Src/Akt-mediated up-regulation in cNOS activation that leads to the apoptotic signal inhibition through the NO-induced caspase-3 S-nitrosylation.


Localized temporal co-delivery of interleukin 10 and decorin genes using amediated by collagen-based biphasic scaffold modulates the expression of TGF-β1/β2 in a rabbit ear hypertrophic scarring model.
Hypertrophic scarring (HS) is an intractable complication associated with cutaneous wound healing. Although transforming growth factor β1 (TGF-β1) has long been documented as a central regulatory cytokine in fibrogenesis and fibroplasia, there is currently no cure. Gene therapy is emerging as a powerful tool to attenuate the overexpression of TGF-β1 and its signaling activities. An effective approach may require transferring multiple genes to regulate different aspects of TGF-β1 signaling activities in a Spatio-temporal manner. Herein we report the additive anti-fibrotic effects of two plasmid DNAs encoding interleukin 10 (IL-10) and decorin (DCN) co-delivered via a biphasic 3D collagen scaffold reservoir platform. Combined gene therapy significantly attenuated inflammation and extracellular matrix components' accumulation in a rabbit ear ulcer model; and suppressed the expressions of genes associated with fibrogenesis, including collagen type I, as well as TGF-β1 and TGF-β2, while enhancing the genes commonly associated with regenerative healing including collagen type III. These findings may serve to provide a non-viral gene therapy platform that is safe, optimized, and effective to deliver multiple genes onto the diseased tissue in a wider range of tissue fibrosis-related maladies.


Risk factors for goiter in a previously iodine-deficient region.
Little information exists from formerly iodine-deficient areas regarding gender-specific risk factors for goiter and their synergisms. The aim of the present study was to investigate such gender-specific risk factors and their interactions in a large population-based sample. The Study of Health in Pomerania (SHIP) comprised 4310 randomly selected participants, aged 20 - 79 years. SHIP was performed in a previously iodine-deficient region. Data from 3915 participants with no known thyroid disorders were analyzed. Goiter was determined by thyroid ultrasound. Sociodemographic characteristics, smoking and alcohol drinking habits, marital status, education level, urine thiocyanate concentrations, and specifically in women, parity and previous or current use of oral contraceptives and hormone replacement therapy, were considered as candidate risk factors for multivariable statistical tests. Only two variables, an advanced age and current smoking, were independently associated with an increased risk for goiter in both genders. Analyses further revealed specific risk factor profiles for goiter which were different among men, pre- and postmenopausal women. We conclude that besides previous iodine deficiency, other risk factors for goiter exist which differ between gender. Among the avoidable risk factors, current smoking was strongly associated with the risk of goiter in men and women. These findings should influence activities which are intended to prevent thyroid disease.


Contour interaction and temporal masking in strabismus and amblyopia.
Visual acuity of amlyopic eyes, measured under binocular viewing conditions, was improved by reducing the contrast of targets presented to the normal eye. Improvement was also obtained by adjusting the temporal relationship between inputs to the normal and amblyopic eye. Optimal acuity was obtained by alternately presenting targets to the two eyes at rates centered about 2 and 7 Hz. These results are interpreted in terms of binocular contour interaction and metacontrast suppression. They suggest that a portion of the amblyope's acuity loss during binocular viewing conditions results from excessive masking by the dominant normal eye.


Inequalities in the distribution of the general practice workforce in England: a practice-level longitudinal analysis.
In England, demand for primary care services is increasing and GP shortages are widespread. Recently introduced primary care networks (PCNs) aim to expand the use of additional practice-based roles such as physician associates (PAs), pharmacists, paramedics, and others through financial incentives for recruitment of these roles. Inequalities in general practice, including additional roles, have not been examined in recent years, which is a meaningful gap in the literature. Previous research has found that workforce inequalities are associated with health outcome inequalities. To examine recent trends in general practice workforce inequalities. A longitudinal study using quarterly General Practice Workforce datasets from 2015-2020 in England. The slope indices of inequality (SIIs) for GPs, nurses, total direct patient care (DPC) staff, PAs, pharmacists, and paramedics per 10 000 patients were calculated quarterly, and plotted over time, with and without adjustment for patient need. Fewer GPs, total DPC staff, and paramedics per 10 000 patients were employed in more deprived areas. Conversely, more PAs and pharmacists per 10 000 patients were employed in more deprived areas. With the exception of total DPC staff, these observed inequalities widened over time. The unadjusted analysis showed more nurses per 10 000 patients employed in more deprived areas. These values were not significant after adjustment but approached a more equal or pro-poor distribution over time. Significant workforce inequalities exist and are even increasing for several key general practice roles, with workforce shortages disproportionately affecting more deprived areas. Policy solutions are urgently needed to ensure an equitably distributed workforce and reduce health inequities.


Nitrogen removal from wastewater using a hybrid membrane-biofilm process: pilot-scale studies.
The hybrid membrane biofilm process (HMBP) is a new approach to achieving total nitrogen removal from wastewater. Air-filled, hollow-fiber membranes are placed into an activated sludge basin and bulk aeration is suppressed. A nitrifying biofilm develops on the membranes, exporting nitrate and nitrite to the bulk liquid. The nitrate and nitrite are reduced by suspended biomass using influent BOD as the electron donor. Previous research demonstrated the HMBP concept at the bench scale and explored process fundamentals. This research explored the HMBP at the pilot scale, with a 120-L reaction tank, real wastewater, and a potentially scalable configuration. Nitrification rates averaged 0.5 g N m(-2)/d(-1), which were lower than found at the bench scale, and lower than predicted by a mathematical model, but still allowed effluent total nitrogen concentrations below 6 mg N/L with an average influent total nitrogen concentration of 25 mg N/L and a hydraulic retention time of 12 hours. More than 75% of the produced nitrate and nitrite was reduced with an average influent sCOD of only 68 mg/L and an average C:N ratio of 3.1. Mass balances on carbon and nitrogen suggest that nitrogen removal via nitrite occurred. This research confirms that the HMBP process is effective for BOD and nitrogen removal from wastewater, and suggests that the grid configuration is viable for scale-up.


Sweat lactate, ammonia, and urea in rugby players.
The purpose of this study was to investigate sweat lactate, ammonia, and urea excretion in rugby players. Fifteen elite amateur rugby players volunteered to participate. The study was conducted during competitive matches in the official season. Plasma and sweat concentrations of lactate, ammonia, and urea were measured before and after the matches. Peak values for creatine kinase activity were observed 24 h after the match. There was no significant change between time points for blood lactate concentration but secretion rate per unit surface and time was significantly reduced after the match. Sweat ammonia concentration increased significantly during the match; values were significantly reduced after 24 h and still remained low at 72 h. Secretion rate was also reduced from 24 h. Urea concentration was significantly reduced at 48 h, while secretion rates decreased at 24 h and 48 h. Lactate in blood was significantly elevated during the match but not thereafter. Blood ammonia was significantly elevated during the match and did not differ from the resting values at 24 or 48 h. Urea in blood tended to decrease during the match, with a significant reduction at 24 h. Significant positive correlations were observed between blood and sweat concentrations for urea and ammonia but not for lactate. Sweat rate correlated positively with sweat lactate secretion. The fact that part of the ammonia formed during exercise is lost with sweat indicates the importance of the purine nucleotide cycle during rugby matches. Our data also confirm that sweat lactate concentration is not influenced by circulatory blood lactate in rugby players.


Supramolecular assembly of an amphiphilic Gd(III) chelate: tuning the reorientational correlation time and the water exchange rate.
We report the synthesis and characterization of the novel ligand H(5)EPTPA-C(16) ((hydroxymethylhexadecanoyl ester)ethylenepropylenetriaminepentaacetic acid). This ligand was designed to chelate the Gd(III) ion in a kinetically and thermodynamically stable way while ensuring an increased water exchange rate (kappa(ex)) on the Gd(III) complex owing to steric compression around the water-binding site. The attachment of a palmitic ester unit to the pendant hydroxymethyl group on the ethylenediamine bridge yields an amphiphilic conjugate that forms micelles with a long tumbling time (tau(R)) in aqueous solution. The critical micelle concentration (cmc = 0.34 mM) of the amphiphilic [Gd(eptpa-C(16))(H(2)O)](2-) chelate was determined by variable-concentration proton relaxivity measurements. A global analysis of the data obtained in variable-temperature and multiple-field (17)O NMR and (1)H NMRD measurements allowed for the determination of parameters governing relaxivity for [Gd(eptpa-C(16))(H(2)O)](2-); this is the first time that paramagnetic micelles with optimized water exchange have been investigated. The water exchange rate was found to be kappa(298)(ex) = 1.7 x 10(8) s(-1), very similar to that previously reported for the nitrobenzyl derivative [Gd(eptpa-bz-NO(2))(H(2)O)](2-) kappa(298)(ex) = 1.5 x 10(8) s(-1)). The rotational dynamics of the micelles were analysed by using the Lipari-Szabo approach. The micelles formed in aqueous solution show considerable flexibility, with a local rotational correlation time of tau(298)(l0) = 330 ps for the Gd(III) segments, which is much shorter than the global rotational correlation time of the supramolecular aggregates, tau(298)(g0) = 2100 ps. This internal flexibility of the micelles is responsible for the limited increase of the proton relaxivity observed on micelle formation (r(1) = 22.59 mM(-1) s(-1) for the micelles versus 9.11 mM(-1) s(-1) for the monomer chelate (20 MHz; 25 degrees C)).


[Pain syndromes of the head, neck and locomotor system--determining current status].
A small series of pain syndrome patients shows that disturbances of the head and neck motor system can lead to various pain syndromes as the vicious circle between pain and muscle tension is initiated by a triggering factor. These pain syndromes include varying combinations of the following symptoms: headache, referred otalgia, arthralgia of the temporomandibular joint, styloid syndrome, tendopathia of the hyoid bone, carotidynia, cervical dysphagia and probably most patients with superior laryngeal nerve neuralgia or glossopharyngeal neuralgia. A detailed differentiation of those syndromes is of little value for diagnostic and therapeutical purposes, because the mixed distribution of the pain irradiation does not indicate the localisation of the primary pathology. The pain syndromes of the head and neck motor system can be caused by temporomandibular joint pathology as well as by anatomical or functional alterations of the cervical spine. Acute exacerbations are triggered off by various influences such as inflammation, trauma, scarring after surgery or radiotherapy. Thus diagnostic and therapeutic measures must take into consideration both the motor system itself and any possible triggering factors. The problem frequently needs interdisciplinary co-operation. An attempt to handle the problem within the boundaries of a single discipline such as ENT, may lead to unnecessary and misleading steps. Guidelines for the management of such pain syndromes are outlined.


USA resistance patterns among UTI pathogens.
The fluoroquinolones are a new, potent class of antimicrobials which are heavily prescribed in the United States. Resistance to these agents has developed primarily in organisms that are inherently less sensitive, such as Staphylococcus spp. and Pseudomonas spp., but also, in some centres, in more sensitive organisms, such as members of the Enterobacteriaceae. Because the fluoroquinolones are a valuable class of broad-spectrum antibiotics, it is desirable that their usefulness be conserved by adopting measures to prevent or minimize the development of resistance. One obvious approach to this is to restrict their use, preventing overuse or misuse. The therapy of urinary tract infections is a major area in which fluoroquinolone usage could be reduced or rationalized. Although these agents are highly efficacious in the therapy of urinary tract infections, so too are older, less expensive agents such as nitrofurantoin, co-trimoxazole, sulphonamides and amoxycillin. From considerations of both economy and minimizing the development of resistance there appears to be little justification for using fluoroquinolones routinely to treat urinary tract infections, except where other oral agents may not be well tolerated or are unlikely to be effective.


Splenic artery aneurysm of the hepatosplenomesenteric trunk.
We herein report the case of a splenic artery aneurysm with a hepatosplenomesenteric trunk that presented in a pregnant woman. Catheter embolization was not performed due to the wide neck of the aneurysm and its close location to the trunk indicates a high risk of mesenteric trunk thrombosis. We instead performed surgical resection of the aneurysm after successful delivery of the infant by Caesarian section. The splenic artery was reconstructed by side-to-end anastomosis with the common hepatic artery.


Personality characteristics of incest survivors on the Draw-A-Person Questionnaire.
We investigated the psychological sequelae of incest through the use of the Draw-A-Person Questionnaire (DAPQ; Karp, 1990), a projective technique with an objective component. A group of adult incest survivors (n = 30) and a matched control sample (n = 30) participated in our study. Ratings of characters drawn by subjects were compared between the two groups on 10 measures hypothesized to differentiate the groups. Results suggest that incest survivors project more negative characteristics on their drawn characters than do control women. In addition, survivors treat their male and female characters differently to a greater extent than do controls. Findings indicate that the DAPQ is a valuable method to detect long-lasting repercussions that may stem from an incestuous experience. Specific differences between the groups are discussed, as well as suggestions for future research.


An in vitro assay of collagen fiber alignment by acupuncture needle rotation.
During traditional acupuncture therapy, soft tissues attach to and wind around the acupuncture needle. To study this phenomenon in a controlled and quantitative setting, we performed acupuncture needling in vitro. Acupuncture was simulated in vitro in three-dimensional, type I collagen gels prepared at 1.5 mg/ml, 2.0 mg/ml, and 2.5 mg/ml collagen, and either crosslinked with formalin or left untreated. Acupuncture needles were inserted into the gels and rotated via a computer-controlled motor at 0.3 rev/sec for up to 10 revolutions while capturing the evolution of birefringence under cross-polarization. Simulated acupuncture produced circumferential alignment of collagen fibers close to the needle that evolved into radial alignment as the distance from the needle increased, which generally matched observations from published tissue explant studies. All gels failed prior to 10 revolutions, and the location of failure was near the transition between circumferential and radial alignment. Crosslinked collagen failed at a significantly lower number of revolutions than untreated collagen, whereas collagen concentration had no effect on gel failure. The strength of the alignment field increased with increasing collagen concentration and decreased with crosslinking. Separate studies were performed in which the gel thickness and depth of needle insertion were varied. As gel thickness increased, gels failed at fewer needle revolutions. For the same depth of insertion, alignment was greater in thinner gels. Alignment increased as the depth of insertion increased. These results indicate that the mechanostructural properties of soft connective tissues may affect their response to acupuncture therapy. The in vitro model provides a platform to study mechanotransduction during acupuncture in a highly controlled and quantitative setting.


Fetal intracranial calcification: pseudo-TORCH phenotype and discussion of related phenotypes.
Fetal intracranial calcification (ICC) noted during antenatal imaging poses a diagnostic challenge. Although this presentation is most commonly associated with intrauterine infection, non-infectious causes of fetal ICC have been reported and include metabolic, genetic, or hemodynamic conditions. We report on a patient with antenatally detected extensive ICC, in whom postnatal imaging revealed a distinctive band-like ICC with abnormal gyral pattern and a negative serology for TORCH infections. Such a constellation of findings have been previously described under the terminology of "pseudo-TORCH phenotype," and we posit that our patient represents this entity. Our patient had unreported dysmorphic features, which expands the phenotypic spectrum of this recently described heterogenous condition. In addition we report on the progression of the phenotype both clinically and radiologically. In view of the limited information available for the differential diagnosis of fetal ICC, we also review the available literature on this topic.


Familial gigantism caused by an NSD1 mutation.
A three-generation family with autosomal dominant segregation of a novel NSD1 mutation (6605G --> A, resulting in Cys2202Tyr) is reported. Haploinsufficiency of NSD1 has been identified as the major cause of Sotos syndrome. The overgrowth condition (MIM 117550) is characterized by facial anomalies, macrocephaly, advanced bone age, and learning disabilities. Manifestations in the present family include dramatically increased height, weight, and head circumference together with a long face, large mandible, and large ears, but mental deficiency was absent.


Rapid detection and quantification of paracetamol and its major metabolites using surface enhanced Raman scattering.
Paracetamol (also known as acetaminophen) is an over-the-counter (OTC) drug that is commonly used as an analgesic for mild pain, headache, cold and flu. While in the short term it is a safe and effective medicine, it is sometimes used for attempted suicides particularly in young adults. In such circumstances it is important for rapid diagnosis of overdoses as antidotes can be given to limit liver damage from one of its primary metabolites N-acetyl-p-benzoquinone imine (NAPQI). Unfortunately, the demand for rapid and sensitive analytical techniques to accurately monitor the abuse of OTC drugs has significantly risen. Ideally these techniques would be highly specific, sensitive, reproducible, portable and rapid. In addition, an ideal point of care (PoC) test would enable quantitative detection of drugs and their metabolites present in body fluids. While Raman spectroscopy meets these specifications, there is a need for enhancement of the signal because the Raman effect is weak. In this study, we developed a surface-enhanced Raman scattering (SERS) methodology in conjunction with chemometrics to quantify the amount of paracetamol and its main primary metabolites (viz., paracetamol sulfate, p-acetamidophenyl β-D-glucuronide and NAPQI) in water and artificial urine. The enhancement of the SERS signals was achieved by mixing the drug or xenometabolites with a gold nanoparticle followed by aggregation with 0.045 M NaCl. We found that the SERS data could be collected directly, due to immediate analyte association with the Au surface and colloid aggregation. Accurate and precise measurements were generated, with a limit of detection (LoD) of paracetamol in water and artificial urine at 7.18 × 10-6 M and 2.11 × 10-5 M, respectively, which is well below the limit needed for overdose and indeed normal levels of paracetamol in serum after taking 1 g orally. The predictive values obtained from the analysis of paracetamol in water and artificial urine were also excellent, with the coefficient of determination (Q2) being 0.995 and 0.996, respectively (1 suggests a perfect model). It was noteworthy that when artificial urine was spiked with paracetamol, no aggregating agent was required due to the salt rich medium, which led to spontaneous aggregation. Moreover, for the xenometabolites of paracetamol excellent LoDs were obtained and these ranged from 2.6 × 10-4 M to 5 × 10-5 M with paracetamol sulfate and NAPQI having Q2 values of 0.934 and 0.892 and for p-acetamidophenyl β-D-glucuronide this was slightly lower at 0.6437.


Enhanced lipid peroxidation and lysosomal enzyme activity in the lungs of rats with prolonged pulmonary deposition of crocidolite asbestos.
The interaction of UICC crocidolite asbestos with biological membranes in vivo was studied in rats after a single intratracheal dose of a suspension of 20 mg of fibres per rat. Development of lung fibrosis (increased level of hydroxyproline, a collagen index together with corresponding pathomorphological alteration) confirmed the penetration of crocidolite fibres into the lungs in the course of seven months exposure. The pulmonary deposition of crocidolite affected the lysosomal membranes of lung cells as manifested by (1) enhanced lipid peroxidation with (2) stimulation (release) of activity of beta-glucuronidase and cathepsin D. Enhanced lipid peroxidation and activity of beta-glucuronidase may contribute to the delayed, carcinogenic effects of crocidolite asbestos.


Efficacy of Antiviral Prophylaxis up to 6 or 12 Months From Completion of Rituximab in Resolved Hepatitis B Patients: A Multicenter, Randomized Study.
Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab. A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin's lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups. In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41-12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4-16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99-26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4-33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999). Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV. ClinicalTrials.gov Identifier: NCT02585947.


Ndr2 Kinase Controls Neurite Outgrowth and Dendritic Branching Through α1 Integrin Expression.
The serine/threonine kinase Ndr2 has been shown to control the inside-out activation of the β1subunit of integrins and the formation of neurites in both primary neurons and neurally differentiated pheochromacytoma (PC12) cells. In this study, we demonstrate that Ndr2 kinase furthermore determines the substrate specificity of neurite extension in PC12 cells via expression of α1β1 integrins. We show that stable overexpression of Ndr2 in PC12 cells increases neurite growth and extension on poly-D-lysine substrate, likely involving an increased expression of active β1 integrin in the growth tips of these cells. By contrast, the Ndr2 overexpressing cells do not show the α1β1 integrin-mediated enhancement of neurite growth on collagen IV substrate that can be seen in control cells. Moreover, they entirely fail to increase in response to activation of α1β1 integrins via a soluble KTS ligand and show a diminished accumulation of α1 integrin in neurite tips, although the expression of this subunit is induced during differentiation to comparable levels as in control cells. Finally, we demonstrate that Ndr2 overexpression similarly inhibits the α1β1 integrin-dependent dendritic growth of primary hippocampal neurons on laminin 111 substrate. By contrast, lack of Ndr2 impairs the dendritic growth regardless of the substrate. Together, these results suggest that Ndr2 regulates α1 integrin trafficking in addition to β1 integrin subunit activation and thereby controls the neurite growth on different extracellular matrix (ECM) substrates.


[Use of Trabecular Bone Score as a complementary approach to DXA for fracture risk assessment in clinical practice].
Physicians can assess the risk of fracture based on bone density (BMD) and several risk factors. Some of them and BMD are incorporated into FRAX, an assessment tool that estimates the 10-years probability of fracture. BMD didn't take into account the microarchitecture. TBS is a texture parameter related to bone microarchitecture. A low TBS is associated with a history of fracture and the incidence of new fracture independently of BMD, clinical risk factors and FRAX. TBS is yet integrated in the FRAX tool, and this effect is of greatest utility for individuals who are close to an intervention threshold. It is particularly useful for the evaluation of secondary osteoporosis, including type 2 diabetes, Gluco-corticoïd induced osteoporosis. It responds to osteoporosis treatments and is not influenced by lumbar degenerative disorders.


Accuracy and results of photopic flash electroretinogram performed with skin electrodes in infants.
As it is not always possible to use corneal electrodes for recording electroretinograms (ERG) in children, it is necessary to check the feasibility of performing ERG with skin electrodes and to try to establish normative data. Fifty-one healthy children (aged 7-11 years) were recruited. Cone ERG and 30-Hz flicker ERG were recorded with one active skin electrode positioned over the lower eyelid and a reference electrode at the outer canthus of the eye. Responses were recorded to full-field stimuli. Correlations between results of both eyes were studied. Results were compared to normative data obtained with corneal electrodes. Cone ERG response was obtained in 100/102 eyes. Flicker ERG was obtained in 88/102 eyes. No correlation between eyes was found for the a-wave latency, the a-wave amplitude, and the latency of the flicker. Mean b-wave implicit time of the cone ERG was 38.71 ± 1.6 ms; the median of its amplitude was 10.0 µV. The median of the amplitude of the flicker ERG was 12.55 µV. Amplitudes are significantly reduced, with a scaling factor of 8.75 for the b-wave amplitude of the cone ERG compared to corneal electrodes (9.6 for the a-wave amplitude and 8.87 for the flicker amplitude). Our study contributes to the establishment of normative data for skin electrode ERG. It emphasizes the feasibility and accuracy of this method. It is very useful to assess the normality of the ERG in many clinical situations, such as nystagmus and suspicion of delayed visual maturation.


Application of the critical angle method to refractive index measurement of human skin in vivo under partial contact.
We adapted the critical angle method for measuring rough surfaces under partial contact to acquire an in vivo skin refractive index (RI). Assuming that the total reflection is the simple sum of reflection from areas that are in contact and reflection from those that are not in contact, the RI can be estimated even for partial contact with a rough surface. We found that cheek skin is sufficiently soft that a sufficiently large area can be in contact and that the critical angle was detectable. The RIs of the cheeks of adult females were measured. The RI range was about 1.51 to 1.53, at a wavelength of 550 nm, without considering systematic errors. The RIs of cheeks are significantly correlated with their conductance, which corresponds to their water content. We determined the relationship between the RI and conductance within the variation of skin under normal conditions; this relationship was theoretically obtained in previous studies. In the present study, a direct in vivo measurement method was developed that enabled us to measure the RI in daily life, although this method contains errors for several reasons, including disregarding absorption.


[Accumulation and release characteristics of heavy metals in Crassostrea rivalaris under mixed exposure].
With a mixed solution of lead (Pb), zinc (Zn), copper (Cu), nickel (Ni), cadmium (Cd), chromium (Cr), mercury (Hg) and arsenic (As), this paper studied the accumulation and release characteristics of test heavy metals in Crassostrea rivalaris. The results showed that C. rivalaris had a strong ability to accumulate Pb, Cu, Ni, Cd, Cr and Hg, being able to indicate the concentration levels of these heavy metals in solution, but a weak ability to accumulate Zn and As. In the following 35 days release stage, no significant change was observed in the contents of test heavy metals in C. rivalaris, suggesting that C. rivalaris had weak ability to release heavy metals. Two-compartment kinetic model could well fit the accumulation of heavy metals in C. rivalaris, but failed in simulating their release characteristics.


Accuracy of diffusion tensor magnetic resonance imaging tractography assessed using intraoperative subcortical stimulation mapping and magnetic source imaging.
Resecting brain tumors involves the risk of damaging the descending motor pathway. Diffusion tensor (DT)-imaged fiber tracking is a noninvasive magnetic resonance (MR) technique that can delineate the subcortical course of the motor pathway. The goal of this study was to use intraoperative subcortical stimulation mapping of the motor tract and magnetic source imaging to validate the utility of DT-imaged fiber tracking as a tool for presurgical planning. Diffusion tensor-imaged fiber tracks of the motor tract were generated preoperatively in nine patients with gliomas. A mask of the resultant fiber tracks was overlaid on high-resolution T1- and T2-weighted anatomical MR images and used for stereotactic surgical navigation. Magnetic source imaging was performed in seven of the patients to identify functional somatosensory cortices. During resection, subcortical stimulation mapping of the motor pathway was performed within the white matter using a bipolar electrode. A total of 16 subcortical motor stimulations were stereotactically identified in nine patients. The mean distance between the stimulation sites and the DT-imaged fiber tracks was 8.7 +/- 3.1 mm (+/- standard deviation). The measured distance between subcortical stimulation sites and DT-imaged fiber tracks combines tracking technique errors and all errors encountered with stereotactic navigation. Fiber tracks delineated using DT imaging can be used to identify the motor tract in deep white matter and define a safety margin around the tract.


Macromolecular requirements for abrogation of Fv-1 restriction by murine leukemia viruses.
The molecular basis of abrogation of Fv-1 restriction in mouse cells by murine leukemia virus was investigated. Two different lines of experimentation indicated that high-molecular-weight viral RNA is required for abrogation. First, the decay of abrogating ability of virus stocks heated at 43 degrees C was quantitatively correlated with a loss of intact virion 35S RNA. Second, Act D virions, which lack such RNA although they contain normal structural proteins, failed to abrogate. These findings imply that abrogation does not result from the mere entry of virion structural proteins into a cell. Additional data indicate that the role of viral RNA in abrogation is not that of a template for DNA synthesis. Virus particles lacking reverse transcriptase activity as a result of either mutation or heat inactivation exhibit abrogating activity even though they do not synthesize detectable viral DNA. In addition, abrogation was shown to take place in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. Thus, abrogation does not depend on viral or cellular DNA synthesis, and the role of viral RNA in this process must involve some other function. The nature of this viral function and its occurrence in Fv-1 permissive cells are discussed.


Complications of uvulopalatopharyngoplasty.
Since the introduction of uvulopalatopharyngoplasty (UVPP) life-threatening complications have been encountered. In our retrospective review of 101 patients undergoing UVPP the overall incidence of early post-operative complications was 25%. One patient died because of post-operative airway obstruction. The risk of early post-operative breathing difficulty was related to the patient's weight, previous heart disease, and severity of OSAS measured by the percentage of obstructive apnoeic episodes and minimum oxygen saturation during sleep. As late as one year after surgery 57% of patients had some kind of problem in relation to the operation, the most common complaint being nasopharyngeal regurgitation (24%). Despite these late complications over 90% of the patients reported improvement in daytime somnolence and snoring.


Urinary incontinence and voiding dysfunction after radical retropubic prostatectomy (prospective urodynamic study).
During this prospective study we analyzed the effects of radical retropubic prostatectomy (RRP) on bladder and sphincter function by comparing preoperative and postoperative urodynamic data. The aim of the study was to determine the reason for urinary incontinence after RRP and explain why one group of patients will be immediately continent after catheter removal, while others need some time to reach complete continence. Urodynamic examination was performed in 63 patients 3-7 days before and 2 months after surgery. Forty-three (68.2%) and 53 (84.1%) patients regained continence at 2 and 9 months following RRP, respectively. Ten patients (15.9%) were immediately continent after catheter removal. Urodynamic stress incontinence was detected in 18 (28.6%), and detrusor overactivity incontinence in 2 (3.2%) patients 2 months after surgery. The amplitude of preoperative maximal voluntary sphincteric contractions was significantly higher in the postoperative continent group (125 vs. 96.5 cmH(2)O, P < 0.0001). The patients who were immediately continent following catheter removal had no lower urinary tract symptoms (LUTS) and urodynamic abnormality preoperatively, and they had significantly higher preoperative and postoperative maximum urethral closure pressure (at rest and during voluntary sphincter contraction) than those who became continent later on. These data suggest that the main cause of incontinence after RRP is sphincteric weakness. In the continent group, those who became immediately continent had significantly higher maximum urethral closure pressure values at rest and at voluntary sphincteric contraction even before the surgery.


Re-evaluation of the first phenytoin paste healing effects on oral biopsy ulcers.
Until now, several formulations of topical phenytoin have been used to promote wound healing. This study was aimed at re-evaluating the effects of a newly formulated phenytoin mucoadhesive paste on wound healing after oral biopsy. In a double-blind clinical trial, 35 consecutive patients with oral lichenoid or lichen planus lesions were randomized into two groups. After incisional biopsy, patients applied simple, or 1% phenytoin paste at least three times a day (after each meal), for 4 days. They were evaluated every other day for size of wound closure, severity of pain, and diameter of the inflammatory halo. This study was approved by Medical Ethics committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran. Statistical analysis was performed using Mann-Whitney U test and Ordinal Logistic Regression. Of 35 patients, 17 (10 [10/17, 59%]) men, 7 (7/17, 41%) women, mean age: 40 (4.11) were in phenytoin group, and 18 (9 [9/9, 50%]) men, 9 (9/9, 50%) women, mean age: 43.1 (5.15) were in placebo group. There were no significant differences between both study groups in terms of age and sex (male/female ratio) (P = 0.76, P = 0.88). As all biopsies were done by means of punch number 8, the incisions were of 10 mm length. After second and third appointments, it was observed that patients in the treatment group showed quicker wound closure and less pain compared to control group significantly (P < 0.05). Although not significant, patients treated with phenytoin paste had smaller inflammatory halo than controls. Applying 1% phenytoin mucoadhesive paste on oral biopsy incisions resulted in accelerated wound healing and decrease in pain.


Highly Sensitive and Stretchable MXene/CNTs/TPU Composite Strain Sensor with Bilayer Conductive Structure for Human Motion Detection.
The universal application of wearable strain sensors in various situations for human-activity monitoring is considerably limited by the contradiction between high sensitivity and broad working range. There still remains a huge challenge to design sensors featuring simultaneous broad working range and high sensitivity. Herein, a typical bilayer-conductive structure Ti3C2Tx MXene/carbon nanotubes (CNTs)/thermoplastic polyurethane (TPU) composite film was developed by a simple and scalable vacuum filtration process utilizing a porous electrospun thermoplastic polyurethane (TPU) mat as a skeleton. The MXene/CNTs/TPU strain sensor is composed of two parts: a brittle densely stacked MXene upper lamella and a flexible MXene/CNT-decorated fibrous network lower layer. Benefiting from the synergetic effect of the two parts along with hydrogen-bonding interactions between the porous TPU fiber mat and MXene sheets, the MXene/CNTs/TPU strain sensor possesses both a broad working range (up to 330%) and high sensitivity (maximum gauge factor of 2911) as well as superb long-term durability (2600 cycles under the strain of 50%). Finally, the sensor can be successfully employed for human movement monitoring, from tiny facial expressions, respiration, and pulse beat to large-scale finger and elbow bending, demonstrating a promising and attractive application for wearable devices and human-machine interaction.


COX-2 and NF-KB overexpression is common in pancreatic cancer but does not predict for COX-2 inhibitors activity in combination with gemcitabine and oxaliplatin.
The attempt to improve therapeutic results in pancreatic carcinoma has recently focused on the emerging role of molecular biology. We investigated the role of COX-2 and NF-KB expression in relation to the use of a COX-2 inhibitor (celecoxib) associated to gemcitabine and oxaliplatin in pancreatic cancer. Forty-four patients with histologically or cytologically verified, locally advanced unresectable and/or metastatic pancreatic carcinoma were eligible for the study. Thirty-three patients (75%) assumed celecoxib for all their treatment period. Treatment was repeated every 2 weeks, until there was evidence of disease progression, patient refusal, or unacceptable toxicity. Efficacy was assessed according to tumor response, clinical benefit, and time-related parameters. Five patients had a partial response, 24 had a stable disease, and 15 had a disease progression, for an overall response rate of 11%. Biochemical response rate based on CA 19.9 levels showed 2 complete and 10 partial responses, whereas 31 patients presented no changes of CA 19.9 levels. COX-2 protein expression was found in 30 tumors, while a moderate or weak/absent expression was present in 10 patients. Sixteen tumors showed a strong expression for NF-KB, 4 a moderate expression, and 5 a weak/absent expression. The use of a COX-2 inhibitor does not add any valuable activity to a gemcitabine/oxaliplatin combination, even in patients with COX-2 and NF-KB overexpressing tumors.


Impact of low-energy shock impulse on nitric oxide serum levels in healthy rabbits.
Nitric oxide (NO) has emerged as a potent effector molecule for a post-resuscitation disease as a result of the low-energy defibrillation. In this article, the authors anlysed the changes of endogenous nitric oxide levels in serum of 35 healthy rabbits after the transthoracic application of low-energy two-phase shock impulse. The animals were randomised into four groups according to the electrical energy dose to be applied during the experiment. Life parameters of the animals were monitored using the BeneViev T5 patient monitor. The nitric oxide concentration in the groups was measured before, 15 and 360 minutes after applying the low-energy two-phase linear electrical impulse. From 15 to 360 minutes the decrease in nitric oxide concentration was observed. The effect was dependent on single impulse and accumulated energy volumes. The highest decrease of NO concentration was observed in 15 minutes following the application of two electrical impulses of accumulated energy of 8 J/kg/bm. After 360 minutes following the application, a significant increase in nitric oxide levels was recorded. The changes in the nitric oxide levels in the blood serum 15 minutes after the defibrillation may initiate the vasomotor disorders as a result of the low-energy influence of the shock impulse.


[Relationship between the thyroid autoimmunity and the risk of preterm birth in pregnant women: a meta-analysis].
To evaluate the relationship between thyroid autoimmunity and the risk of preterm birth. Literature search was done among PubMed, Embase, Wanfang Medical Database, China Academic Journal Network Publishing Database and China Biology Medicine disc from Jan. 1(st) 1980 to July 31(st), 2015. (1) Literature were extracted according to inclusion and exclusion standards, and the quality of the extracted literature were evaluated by Newcastle-Ottawa Scale (NOS). (2) Meta-analysis was performed by RevMan 5 software formulated by using the Cochrane library databases. Various heterogeneity of the research was inspected firstly. According to the results of the inspection a certain effect model was selected (including fixed effects model, the random effects model) to be utilized in merger analysis. In this study pregnant women with both thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin (TG-Ab) positive were defined as thyroid antibody positive pregnant women. Pregnant women with only TPO-Ab positive were defined as TPO-Ab positive pregnant women. Then the relationship of antibody positive and the risk of a preterm birth was analyzed respectively. (1) Ten cohort studies were enrolled, of which NOS scale score were 7 or higher. All the studies are of medium quality and above. A total of 1 322 cases of preterm birth occurred among 19 910 pregnant women. (2) Positive thyroid autoantibodies did not increase the risk of preterm birth in euthyroid pregnant women (OR=1.41, 95%CI: 0.83-2.40, P=0.200) or in pregnant women with hypothyroidism (OR=0.68, 95% CI: 0.32-1.44, P=0.310) . Positive TPO-Ab in euthyroid pregnant women increase the risk of preterm birth significantly (OR=2.08, 95%CI: 1.09-3.97, P=0.030), but positive TPO-Ab in pregnant women with hypothyroidism did not increase the risk of preterm birth significantly (OR=1.21, 95%CI: 0.65-2.24, P=0.550). Positive TPO-Ab is an independent risk factor of preterm birth in euthyroid pregnant women.


Applying Quantitative Molecular Tools for Virus Transport Studies: Opportunities and Challenges.
Bacteriophages have been used in soil column studies for the last several decades as surrogates to study the fate and transport behavior of enteric viruses in groundwater. However, recent studies have shown that the transport behavior of bacteriophages and enteric viruses in porous media can be very different. The next generation of virus transport science must therefore provide more data on mobility of enteric viruses and the relationship between transport behaviors of enteric viruses and bacteriophages. To achieve this new paradigm, labor intensity devoted to enteric virus quantification method must be reduced. Recent studies applied quantitative polymerase chain reaction (qPCR) to column filtration experiments to study the transport behavior of human adenovirus (HAdV) in porous media under a variety of conditions. A similar approach can be used to study the transport of other enteric viruses such as norovirus. Analyzing the column samples with both qPCR and culture assays and applying multiplex qPCR to study cotransport behavior of more than one virus will provide information to under-explored areas in virus transport science. Both nucleic acid extraction kits and one-step lysis protocols have been used in these column studies to extract viral nucleic acid for qPCR quantification. The pros and cons of both methods are compared herein and solutions for overcoming problems are suggested. As better understanding of the transport behavior of enteric viruses is clearly needed, we strongly advocate for application of rapid molecular tools in future studies as well as optimization of protocols to overcome their current limitations.


Ten Daily Fractions for Whole Breast Cancer Irradiation: Long Term Results.
To report the feasibility and oncological outcomes in breast cancer patients treated with a short hypofractionated radiotherapy schedule. We evaluated 380 breast cancer patients treated with ten daily fractions of radiotherapy up to 39 Gy on tumor bed. Primary endpoint was local relapse rate (LRR). Secondary endpoints were overall survival (OS) and metastasis-free survival (MFS). The median follow up was 5.0 years. Two- and 5-year LRR rates were 0.2 and 2%, respectively. Two- and 5-year MFS rates were 96.1% and 90.5%, respectively. Two and 5-year OS rates were 97.4% and 95%, respectively. This short schedule may represent an alternative option to standard mild hypofractionated radiotherapy in breast cancer patients due to its excellent feasibility and very low recurrence rate.


Predictors of severe tricuspid regurgitation in patients with permanent pacemaker or automatic implantable cardioverter-defibrillator leads.
Patients with permanent pacemaker or automatic implantable cardioverter-defibrillator (AICD) leads have an increased prevalence of tricuspid regurgitation. However, the roles of cardiac rhythm and lead-placement duration in the development of severe tricuspid regurgitation are unclear. We reviewed echocardiographic data on 26 consecutive patients who had severe tricuspid regurgitation after permanent pacemaker or AICD placement; before treatment, they had no organic tricuspid valve disease, pulmonary hypertension, left ventricular dysfunction, or severe tricuspid regurgitation. We compared the results to those of 26 control subjects who had these same devices but no more than mild tricuspid regurgitation. The patients and control subjects were similar in age (mean, 81 ±6 vs 81 ±8 yr; P = 0.83), sex (male, 42% vs 46%; P = 0.78), and left ventricular ejection fraction (0.60 ±0.06 vs 0.58 ± 0.05; P = 0.4). The patients had a higher prevalence of atrial fibrillation (92% vs 65%; P=0.01) and longer median duration of pacemaker or AICD lead placement (49.5 vs 5 mo; P < 0.001). After adjusting for age, sex, and right ventricular systolic pressure by multivariate logistic regression analysis, we found that atrial fibrillation (odds ratio=6.4; P = 0.03) and duration of lead placement (odds ratio=1.5/yr; P = 0.001) were independently associated with severe tricuspid regurgitation. Out study shows that atrial fibrillation and longer durations of lead placement might increase the risk of severe tricuspid regurgitation in patients with permanent pacemakers or AICDs.


Mechanism- and experience-based strategies to optimize treatment response to the capsaicin 8% cutaneous patch in patients with localized neuropathic pain.
The capsaicin 8% cutaneous patch is an emergent new treatment option for patients with peripheral neuropathic pain. In randomized controlled clinical studies relevant pain relief for 12 weeks was achieved in about one third of patients following a single application. The first part of this paper is a review of the pathophysiology, pharmacology, and published clinical trials with the capsaicin 8% cutaneous patch. The second part reports on outcomes of an interdisciplinary expert workshop, where new treatment results of three major German pain centers were presented and reviewed with the objectives of obtaining responder rates for different pain syndromes, assessing maintenance of effect under real-life conditions, and giving recommendations for practical care. The 12 week responder rates with pain relief of ≥ 30% were comparable in patients with mononeuropathies (37.9%) and postherpetic neuralgia (38.8%). Similar responder rates were seen in a subgroup of patients with cervical spine radiculopathy and back pain (46.7%). In HIV-associated neuropathy the responder rates were high (47.8%) but lower in patients with other polyneuropathies (17.6%). Response rates were nearly identical after 1 week (46.6%) and 4 weeks (43.3) and dropped only slightly at 12 weeks (37.4%). In a subgroup of 54 patients who underwent a second treatment, efficacy was maintained. Response rates in patients with or without lidocaine pretreatment were comparable. Treatment with the capsaicin 8% cutaneous patch was generally safe and well tolerated. The workshop panel recommended further investigation of opportunities to improve the application procedure and to perform studies on the skin penetration and distribution of capsaicin. A modified quantitative sensory testing (QST) should be developed for clinical practice in order to better understand the correlation of sensory profiles and response to capsaicin treatment.


Chemokine CXCL7 Heterodimers: Structural Insights, CXCR2 Receptor Function, and Glycosaminoglycan Interactions.
Chemokines mediate diverse fundamental biological processes, including combating infection. Multiple chemokines are expressed at the site of infection; thus chemokine synergy by heterodimer formation may play a role in determining function. Chemokine function involves interactions with G-protein-coupled receptors and sulfated glycosaminoglycans (GAG). However, very little is known regarding heterodimer structural features and receptor and GAG interactions. Solution nuclear magnetic resonance (NMR) and molecular dynamics characterization of platelet-derived chemokine CXCL7 heterodimerization with chemokines CXCL1, CXCL4, and CXCL8 indicated that packing interactions promote CXCL7-CXCL1 and CXCL7-CXCL4 heterodimers, and electrostatic repulsive interactions disfavor the CXCL7-CXCL8 heterodimer. As characterizing the native heterodimer is challenging due to interference from monomers and homodimers, we engineered a "trapped" disulfide-linked CXCL7-CXCL1 heterodimer. NMR and modeling studies indicated that GAG heparin binding to the heterodimer is distinctly different from the CXCL7 monomer and that the GAG-bound heterodimer is unlikely to bind the receptor. Interestingly, the trapped heterodimer was highly active in a Ca2+ release assay. These data collectively suggest that GAG interactions play a prominent role in determining heterodimer function in vivo. Further, this study provides proof-of-concept that the disulfide trapping strategy can serve as a valuable tool for characterizing the structural and functional features of a chemokine heterodimer.